Abstract

The effects of tyramine and cocaine on catecholamine concentrations in subcellular fractions of the isolated, perfused cat heart (Langendorff preparation) were studied. Centrifugation of atrial and left ventricular homogenates at 2000 x g for 5 minutes provided a sediment ("coarse" fraction) and a supernatant fraction. The latter was then centrifuged at 105,000 x g for 60 minutes to yield a sediment ("particulate" fraction) and a "soluble," supernatant, fraction.

Whereas perfusion of the heart for 90 minutes with nondrug containing solution caused significant depletion of catecholamines in both "particulate" and "soluble" fractions in the ventricle, depletion of only the "soluble" fraction was observed in the atria. Sufficiently high concentrations of cocaine prevented this depletion and decreased cardiac rate.

Low concentrations of tyramine induced significant depletion of catecholamines in both "soluble" and "particulate" fractions of atria and left ventricle within 30 minutes. Higher concentrations caused more marked depletion of the "particulate" fraction. Cocaine had a biphasic effect on catecholamine levels. Low concentrations of the drug induced significant depletion of amines in the "soluble" and "particulate" fractions of the ventricle but only in the "soluble" fraction of the atria. High concentrations prevented the spontaneous loss of amines which occurs during perfusion in the absence of any drug and antagonized the depleting action of tyramine. Studies in which the concentration of either tyramine or cocaine was varied and the other maintained constant suggest that the primary effect of tyramine is a mobilization of catecholamines from the "soluble" fraction. A reversible, dose-dependent antagonism between the two drugs was observed.